Inhibition by human leukocyte elastase of neutrophil-mediated platelet activation

Abstract

When human polymorphonuclear neutrophils and platelets were incubated with human leukocyte elastase before N-formyl-Met-Leu-Phe (FMLP) challenge, a time- and concentration-dependent inhibition of the resulting platelet activation was observed. Thus, when the mixed cell suspension was preincubated for 6 min with 1 μM elastase before stimulation of neutrophils with 0.5 μM FMLP, resulting aggregations and serotonin releases were reseectively only 4.4±4.1% (n=4 and 1.6±2.4% (n=4) as compared to 41.6±5.2% (n=9) and 71.3±16.0 (n=9) for controls. A direct inhibitory action of clastase on neutrophil activation was ruled out, as well as a breakdown of cathepsin G, a mediator involved in neutrophil-mediated platelet activation. In fact, we demonstrated that the target for the inhibitory effect of elastase in such a cell-to-cell cooperation system was the platelet. This phenomenon is likely to play a role under in vivo conditions in pathologies in which a significant granulocytic proteolytic activity has been detected in the plasma.